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==Overview==
==Overview==
Follicular thyroid cancer arises from follicular cells of thyroid, which are secretory cells that are normally involved in production and secretion of thyroid hormones thyroxine (T4)and triiodothyronine (T3). Genes involved in the pathogenesis of Follicular thyroid cancer include ''Ras'', ''PAX8/PPARγ'', and ''PTEN''.
Follicular thyroid cancer arises from [[Follicular cell|follicular cells]] of [[thyroid]], which are [[Secretion|secretory]] [[Cell (biology)|cells]] that are normally involved in production and [[secretion]] of [[thyroid hormones]], [[thyroxine|thyroxine (T4)]] and [[Triiodothyronine|triiodothyronine (T3)]]. [[Gene|Genes]] involved in the [[pathogenesis]] of follicular thyroid cancer include [[Ras|''RAS'']], ''[[PAX8 gene|PAX8]]/[[Peroxisome proliferator-activated receptor|PPARγ]]'', and [[PTEN|''PTEN'']].
==Pathogenesis==
==Pathogenesis==
* Follicular thyroid cancer is the second most common type of cancer. It constitute about 15% of thyroid cancers.
* Follicular thyroid cancer is the second most common type of [[cancer]]. It constitutes about 15% of [[Thyroid cancer|thyroid cancers]].
[[File:Follicular thyroid carcinoma pathogenesis.png|thumb|center|800px|Pathogenesis of follicular thyroid carcinoma]]
[[File:Follicular thyroid carcinoma pathogenesis 2.0.jpg|thumb|left|700px|Pathogenesis of follicular thyroid carcinoma]]
* This occurs more commonly in women of over 50 years old. [[Thyroglobulin]] (Tg) can be used as a [[tumor marker]] for well-differentiated follicular thyroid cancer. Follicular carcinoma tends to metastasize to the lungs and bone via the bloodstream, while papillary thyroid carcinoma commonly metastasizes to cervical lymph nodes.Unlike papillary it metastasises late to lymph nodes, with only 5-10% of patients having nodal metastases at the time of diagnosis. Haematogenous spread is however much more common with 20% or so of patients having distant haematogenous metastases at presentation.<ref name=Radiopaedia 2015 Papillary thyroid cancer
<br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br>
>{{cite web | title = Radiopedia 2015 Follicular thyroid cancer [Dr Matt A. Morgan and Dr Frank Gaillard]| url = http://radiopaedia.org/articles/follicular-thyroid-cancer }}</ref>
* Follicular thyroid cancer occurs more commonly in women over 50 years of age.
* [[Thyroglobulin|Thyroglobulin (Tg)]] can be used as a [[tumor marker]] for well-differentiated follicular thyroid cancer.
* Follicular carcinoma tends to [[Metastasis|metastasize]] to the [[lung]]s and [[bone]] via the [[bloodstream]].
*Follicular thyroid cancer [[Metastasis|metastasizes]] to [[lymph node|lymph nodes]] late in the course of the [[disease]], with only 5 - 10% of [[Patient|patients]] having [[Lymph node|nodal]] [[metastases]] at the time of [[diagnosis]].  
*Hematogenous spread is however much more common with 20% of the [[Patient|patients]] having distant hematogenous [[Metastasis|metastases]] at at the time of [[diagnosis]].<ref 2015="" name="Radiopaedia" papillary="" thyroid="" cancer="">{{cite web | title = Radiopedia 2015 Follicular thyroid cancer [Dr Matt A. Morgan and Dr Frank Gaillard]| url = http://radiopaedia.org/articles/follicular-thyroid-cancer }}</ref>
* A [[Hurthle cells|Hürthle cell]] (also known as Askanazy [[Cell (biology)|cell]]) is an [[large cell|oncocytic cell]] in the [[thyroid]] that is often associated with [[Hashimoto's thyroiditis]] as well as follicular thyroid cancer.<ref name="Hurthle Cell Carcinoma">{{cite web|url=http://www.emedicine.com/med/topic1045.htm |title=Hurthle Cell Carcinoma |author=Aytug, Serhat |publisher=[[eMedicine]] |date=[[June 13]], 2006}}</ref>
 
==Genetics==
==Genetics==
* The ''Ras'' oncogene is positive in a significant proportion of individuals. Ras oncogene act through the RAF-MEK-MAPK kinase pathway.
* The [[ras|''Ras'' oncogene]] is positive in a significant proportion of individuals.<ref name="pmid123644662">{{cite journal |vauthors=Martelli ML, Iuliano R, Le Pera I, Sama' I, Monaco C, Cammarota S, Kroll T, Chiariotti L, Santoro M, Fusco A |title=Inhibitory effects of peroxisome poliferator-activated receptor gamma on thyroid carcinoma cell growth |journal=J. Clin. Endocrinol. Metab. |volume=87 |issue=10 |pages=4728–35 |date=October 2002 |pmid=12364466 |doi=10.1210/jc.2001-012054 |url=}}</ref>
* Other genes involved in the pathogenesis of follicular thyroid cancer are as follows:
*The [[ras|''Ras'' oncogene]] acts through the RAF-MEK-MAPK kinase pathway.
:* RET/PTC (translocation) associated with MAPK and PI3K-AKT signaling pathways
* Other [[gene|genes]] involved in the [[pathogenesis]] of follicular thyroid cancer are:<ref name="pmid12866375">{{cite journal |vauthors=Zhu Z, Gandhi M, Nikiforova MN, Fischer AH, Nikiforov YE |title=Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations |journal=Am. J. Clin. Pathol. |volume=120 |issue=1 |pages=71–7 |date=July 2003 |pmid=12866375 |doi=10.1309/ND8D-9LAJ-TRCT-G6QD |url=}}</ref>
 
:*''[[RET gene|RET]]/[[PTC]]'' ([[translocation]]) associated with [[Mitogen-activated protein kinase|MAPK]] and [[Phosphoinositide 3-kinase|PI3K]]-[[AKT]] signaling pathways.


:* ''HRAS, KRAS, NRAS'' (mutation) associated with MAPK and PI3K-AKT signaling pathways
:*[[HRAS|''HRAS'']], [[KRAS|''KRAS'']], [[Neuroblastoma RAS viral oncogene homolog|''NRAS'']] ([[mutation]]) associated with [[mitogen-activated protein kinase]] and [[Phosphoinositide 3-kinase|PI3K]]-[[AKT]] signaling pathways.


:* ''PAX8/PPARγ'' (translocation) associated with PAX8-associated nuclear transcription signaling pathways. ''PAX8'' is responsible for follicular cell differentiation.
:*''[[PAX8 gene|PAX8]]/[[Peroxisome proliferator-activated receptor|PPARγ]]'' ([[translocation]]) associated with [[PAX8|''PAX8'']]-associated [[Cell nucleus|nuclear]] [[Transcription (genetics)|transcription]] signaling pathways. [[PAX8|''PAX8'']] is responsible for the [[Thyroid epithelial cell|follicular cell]] differentiation.


:* ''PTEN'' (mutation) associated with PI3K-AKT signaling pathways
:*[[PTEN|''PTEN'']] ([[mutation]]) associated with [[Phosphoinositide 3-kinase|PI3K]]-[[AKT]] signaling pathways.


:* ''PTEN'' (deletion) associated with PI3K-AKT signaling pathways
:*[[PTEN|''PTEN'']] ([[Deletion (genetics)|deletion]]) associated with [[Phosphoinositide 3-kinase|PI3K]]-[[AKT]] signaling pathways.


:* ''IDH1'' (mutation) assciated with IDH1-associated metabolic pathways signaling pathways
:*''[[IDH1]]'' ([[mutation]]) assciated with [[IDH1]]-associated [[Metabolism|metabolic]] pathways signaling pathways.
:* Phosphatase and tensin homologue suppressor gene and the phosphatidylinositol 3-kinase pathway are also involved in the pathogenesis of follicular thyroid tumor.
*[[Phosphatase]] and tensin homologue suppressor [[gene]] and the [[Phosphoinositide 3-kinase|phosphatidylinositol 3-kinase]] pathway are also involved in the [[pathogenesis]] of follicular thyroid tumor.
:* ''p53'', ''c-myc'', ''c-fos'', and the thyrotropin (TSH) receptor are some other factors involved in the pathogenesis of follicular thyroid cancer.
* [[P53 (protein)]], [[Myc|''c-myc'']], [[C-Fos|''c-fos'']], and the [[Thyroid-stimulating hormone|thyrotropin (TSH)]] [[Receptor (biochemistry)|receptor]] are some other factors involved in the [[pathogenesis]] of follicular thyroid cancer.
:* MicroRNAs namely miR-192, miR-197, miR-328, and miR-346 have increased expression in follicular cell carcinoma.
* [[microRNA|MicroRNAs]] namely miR-192, miR-197, miR-328, and miR-346 have increased expression in follicular cell carcinoma.
[[File:Thyroid cancer carcinogensis.jpg|thumb|center|Schema of key pathways in the development and progression of thyroid cancer.]]
[[File:Thyroid cancer carcinogensis.jpg|thumb|center|Schema of key pathways in the development and progression of thyroid cancer.]]


==Associated Conditions==
==Associated Conditions==
* Cowden disease
* [[Cowden disease]]
* Carney complex, type I
* [[Carney complex]], type I


==Gross Pathology==
==Gross Pathology==
* Encapsulated tumors
* Encapsulated tumors
[[Image:Follicular adenoma of the thyroid.jpg|thumb|center|Gross pathological section of a follicular thyroid carcinoma (tumor at the bottom).]]
[[File:Folladen.jpg|thumb|left|Gross pathological section of a follicular thyroid carcinoma (tumor at the bottom).]]
<br style="clear:left">
 
==Microscopic Pathology==
==Microscopic Pathology==
* It is not possible to distinguish between follicular adenoma and carcinoma on cytological grounds. If fine needle aspiration cytology (FNAC) suggests follicular neoplasm, thyroid lobectomy should be performed to establish the [[Histopathology|histopathological]] diagnosis.
 
* Trabecular, solid, follicular tumor cells that invade tumor capsule or surrounding vascular structures
* On [[Microscopy|microscopic examination]], [[Trabeculae|trabecular]], solid, [[Follicular cell|follicular]] [[Tumor cell|tumor cells]] that [[Invasion|invade]] [[capsule|tumor capsule]] or surrounding [[Vessels|vascular structures]], are found.
<gallery>
<gallery>
Image:Follicular thyroid cancer 01.png|Thyroid, total thyroidectomy. Widely invasive follicular carcinoma, 4.5 cm, with lymphovascular invasion and extracapsular extension. Negative margins
Image:Metastatic follicular thyroid carcinoma - Case 264 (8558730243).jpg|Metastatic follicular thyroid carcinoma<ref>http://librepathology.org/wiki/index.php/File:Metastatic_follicular_thyroid_carcinoma_-_Case_264_(8558730243).jpg Accessed on October, 29 2015</ref>
Image:Lymph node FNAC metastatic follicular carcinoma.png|Lymph node FNA showing metastatic follicular carcinoma.
Image:Metastatic follicular thyroid carcinoma - Case 264.jpg|Metastatic follicular thyroid carcinoma<ref>http://librepathology.org/wiki/index.php/File:Metastatic_follicular_thyroid_carcinoma_-_Case_264_(8559837390).jpg  Accessed on October, 29 2015</ref>
Image:Lymphnode FNAC metastatic follicular carcinoma 02.png|Lymph node FNA showing metastatic follicular carcinoma.
Image:FNAC lymph node metastatic follicular carcinoma 03.png|Lymph node FNA showing metastatic follicular carcinoma
Image:Metastatic follicular carcinoma in the bone.png|C1 vertebrae biopsy positive for metastatic follicular carcinoma
Image:Metastatic follicular cancer in the bone.png|C1 vertebrae biopsy positive for metastatic follicular carcinoma
Image:Metastatic follicular thyroid carcinoma - Case 264 (8558730243).jpg|Metastatic follicular carcinoma
Image:Metastatic follicular thyroid carcinoma - Case 264.jpg|Metastatic follicular carcinoma
</gallery>
</gallery>
==Histopathological Video==
===Video===
===Video===
{{#ev:youtube|3_eCHeOkdgg}}
{{#ev:youtube|3_eCHeOkdgg}}
==References==
==References==
{{Reflist|2}}
{{Reflist|2}}


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Latest revision as of 17:48, 29 October 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Overview

Follicular thyroid cancer arises from follicular cells of thyroid, which are secretory cells that are normally involved in production and secretion of thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Genes involved in the pathogenesis of follicular thyroid cancer include RAS, PAX8/PPARγ, and PTEN.

Pathogenesis

  • Follicular thyroid cancer is the second most common type of cancer. It constitutes about 15% of thyroid cancers.
Pathogenesis of follicular thyroid carcinoma





























Genetics

Schema of key pathways in the development and progression of thyroid cancer.

Associated Conditions

Gross Pathology

  • Encapsulated tumors
Gross pathological section of a follicular thyroid carcinoma (tumor at the bottom).


Microscopic Pathology

Histopathological Video

Video

{{#ev:youtube|3_eCHeOkdgg}}

References

  1. Aytug, Serhat (June 13, 2006). "Hurthle Cell Carcinoma". eMedicine. Check date values in: |date= (help)
  2. Martelli ML, Iuliano R, Le Pera I, Sama' I, Monaco C, Cammarota S, Kroll T, Chiariotti L, Santoro M, Fusco A (October 2002). "Inhibitory effects of peroxisome poliferator-activated receptor gamma on thyroid carcinoma cell growth". J. Clin. Endocrinol. Metab. 87 (10): 4728–35. doi:10.1210/jc.2001-012054. PMID 12364466.
  3. Zhu Z, Gandhi M, Nikiforova MN, Fischer AH, Nikiforov YE (July 2003). "Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations". Am. J. Clin. Pathol. 120 (1): 71–7. doi:10.1309/ND8D-9LAJ-TRCT-G6QD. PMID 12866375.
  4. http://librepathology.org/wiki/index.php/File:Metastatic_follicular_thyroid_carcinoma_-_Case_264_(8558730243).jpg Accessed on October, 29 2015
  5. http://librepathology.org/wiki/index.php/File:Metastatic_follicular_thyroid_carcinoma_-_Case_264_(8559837390).jpg Accessed on October, 29 2015